This grant propose five years of research to investigate the abuse liability of d-amphetamine, an indirect dopamine agonist, in high and low sensation-seeking humans. Previous research has established a positive relationship between the personality factor, sensation-seeking, and both frequency and quantity of drug use. Based in part on this evidence, prevention efforts that focus on high sensation seekers are being developed. Recent experimental investigations using an animal model of novelty seeking behavior have demonstrated that differences in the behavioral effects of drugs with abuse liability between high and low novelty-seeking organism s are associated with differences in dopamine system activity. Studies in this application will directly test for differences in drug abuse liability between high and low sensation seeking humans. In addition, these studies will assess whether individual differences in abuse liability between high- and low sensation seekers are associated with dopamine system activity. The existing Lexington Longitudinal Database will be used to identify young adults (over age 18) who have consistently scored in the upper third (high sensation seeking, and lower third (low sensation seekers) of their age-based cohort during four consecutive annual assessments on a modified Zuckerman sensation- seeking scale between their sixth and ninth grade school years. In three separate studies, differences between high and low sensation seekers in 1) the discriminative effects of amphetamine, (as well as the extent to which th discriminative stimulus effects of amphetamine generalize selectively to other dopamine agonists and/or are blocked by haloperidol, a dopamine antagonist), 2) the reinforcing effects of amphetamine, and 3) the performance an physiological effects of amphetamine, methylphenidate and diazepam will be determined. Standardized and validated procedures that are commonly used in the assessment of drug abuse liability in humans will be employed in these studies. In addition, reliable and substantial group differences on the sensation-seeking factor will be insured, as a result of the availability of the Lexington longitudinal Database. As such, a clear test of the relationship between sensation-seeking and drug abuse liability will be obtained in these studies. The wealth of data available in the lexington longitudinal Database (e.g., peer associations, school performance, prior drug use, family status, other intrapersonal factors) will also be available to examine individual differences in drug abuse liability, in addition to sensation seeking status. he results of these studies will directly assess the efficacy of sensation-seeking as a predictor of risk for drug abuse liability, and may have important implications for understanding individual differences in drug abuse liability.